Since the identification of the TMPRSS2-ERG rearrangement as the most common fusion event in prostate cancer, various methods have been developed to detect this rearrangement and to study its prognostic significance. We report a novel four-color fluorescence in situ hybridization (FISH) assay that detects not only the typical TMPRSS2-ERG fusion but also alternative rearrangements of the TMPRSS2 or ERG gene. We validated this assay on fresh, frozen, or formalin-fixed paraffin-embedded prostate cancer specimens, including cell lines, primary prostate cancer tissues, xenograft tissues derived from metastatic prostate cancer, and metastatic tissues from castration-resistant prostate cancer (CRPC) patients. When compared with either reverse transcription-polymerase chain reaction or the Gen-Probe method as the technical reference, analysis using the four-color FISH assay demonstrated an analytical sensitivity of 94.5% (95% confidence interval [CI] 0.80-0.99) and specificity of 100% (95% CI 0.89-1.00) for detecting the TMPRSS2-ERG fusion. The TMPRSS2-ERG fusion was detected in 41% and 43% of primary prostate cancer (n = 59) and CRPC tumors (n = 82), respectively. Rearrangements other than the typical TMPRSS2-ERG fusion were confirmed by karyotype analysis and found in 7% of primary cancer and 13% of CRPC tumors. Successful karyotype analyses are reported for the first time on four of the xenograft samples, complementing the FISH results. Analysis using the four-color FISH assay provides sensitive detection of TMPRSS2 and ERG gene rearrangements in prostate cancer.
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